Malaria in Children with Sickle Cell Anaemia in Areas with Low, Moderate and High Transmission in Uganda

Background. Few large prospective studies have evaluated burden and outcomes of malaria in children with sickle cell anaemia (SCA) in malaria endemic countries. We evaluated the incidence, complications and outcome of malaria in three cohorts of Ugandan children with SCA in three areas with differing malaria transmission. Methods. Cohort 1 were SCA aged 3-9 years, enrolled in the hydroxyurea therapy for neurological and cognitive protection in Uganda (BRAINSAFE II) trial at Mulago Hospital, a low transmission area, while cohort 2 and 3 aged 6 months to 15 years, were enrolled in the dihydroartemisinin-piperaquine (DP) or sulphadoxine-pyrimethamine (SP) for the chemoprevention of malaria in SCA (CHEMCHA) trial at Jinja Hospital (moderate transmission) and Kitgum Hospital (high transmission). In cohort 1, all received SP for malaria chemoprophylaxis and hydroxyurea at 20-30mg/kg/day, while cohorts 2 and 3, received either DP or SP for malaria chemoprevention, and a proportion (10%) received hydroxyurea in the study. Results. A total of 706 participants were enrolled: 267, 249 and 190 at Mulago, Jinja and Kitgum respectively. The mean age was 6.5 (SD 3.4) years; 5.1 (1.7), 7.9 (4.3) and 6.8 (3.5) years for Mulago, Jinja, and Kitgum respectively. Incidence of malaria was 13 (95% CI 6, 20) per 100 child years in low, 38 (95% CI 26, 51) in moderate and 104 (95% CI 64, 144) in the high transmission area, p<0.001. Adjusting for hydroxyurea treatment, incidence of malaria was 33 (95%CI 14, 52) per 100 child year on hydroxyurea and 51 (95%CI 40, 62) per 100 child years without hydroxyurea, p=0.001. The most common SCA-related complications were anaemia (39.6%, 133/336), and pain (27.7%, 93/336) among children with malaria. Over a period of 1042.8 person years, there were 115 admissions for malaria, with an overall incidence of 11 per 100 child year (95% CI 9, 13), and this differed across sites, p<0.001. Overall, 1.5% (11/706) children died, and 18.2% (2/11) deaths were directly related to malaria infection. Conclusion. Malaria incidence remains high among Ugandan children with SCA, and differs by transmission patterns. Prevention strategies should be strengthened, especially in high transmission areas